Project Summary Early stages of neural processing are informed by later stages, and this descending control plays multiple, important roles. Among sensory systems, descending control in the auditory system is probably most complex, and therefore least understood. The olivocochlear efferent system is a reflex pathway that modifies the response of the organ of Corti to acoustic signals. Here we focus on the medial olivocochlear system (MOC), which through a sophisticated cholinergic mechanism protects against acoustic damage and enhances the ability of the cochlea to detect signals in noise. MOC cells receive glutamatergic reflex input from cochlear nucleus but also descending input from cortex and midbrain. Moreover, MOC neurons excited by acetylcholine receptor agonists suggesting local cholinergic influences. How these distinct inputs function relative to one another is unknown. Indeed, the literature has not clarified functional differences in these inputs because of limitations in the classical physiological or anatomical approaches to independently activate different neural pathways to the MOC neurons. Here we propose to use modern mouse genetic and optogenetic techniques combined with electrophysiology in a brain slice system to determine the intrinsic and synaptic properties that underlie olivocochlear function. An additional point of control of MOC system is through MOC collaterals made in the cochlear nucleus, which ultimately feeds back to MOC cells. How cholinergic signaling from MOC and from midbrain pedunculopontine tegmental controls the MOC is unknown. A working hypothesis is that MOC and PPT act on distinct microcircuits in cochlear nucleus and that this translates to differential feedback control to MOC via the IC. This will be tested here using electrophysiological and optogenetic analysis of cholinergic influences in the cochlear nucleus in vitro and in vivo. Because the MOC system plays an essential in protection against noise damage, it is likely that the results of this study will lead to a better means to prevent damage to, or recover, human hearing.